The proposed research aims to study the mechanisms involved in primary demyelination. The lipid and protein constituents of the myelin membrane will be labeled with specific isotopes and the loss of these labeled constituents from the myelin membrane during demyelination in experimental allergic encephalomyelitis will be measured to determine the sequence of breakdown of the myelin membrane. A second series of experiments using double-label techniques will be accomplished to confirm the studies done with a single label, as well as to be able to reduce the possible errors involved in the recovery of a subcellular fraction such as myelin. Certain acid hydrolytic enzymes involved in the degradation of proteins and lipids will be measured during various stages of demyelination to determine their role in the breakdown of the myelin sheath. If there are changes in enzyme activity it will be possible to determine if the activities are the result of increased catabolism in the oligodendrocyte or to the invading macrophage.